The major objective of the proposed research is to elucidate the mechanism of the immunological impairment of the myeloma bearing host by isolating and characterizing the immunosuppressive soluble factors and by identifying the suppressive cell (B or T cell, macrophage or other). In order to achieve these goals, we will 1) Study the suppressive activity of serum or ascites from tumor-bearing mice and/or of cell extracts of lymphoid tissue; 2) Identify the suppressor cell by in vivo transfer experiments and by in vitro co-culturing experiments; 3) Isolate and characterize the suppressive factor by column chromatography (Sephadex G-200, DEAE - Sephadex); 4) Compare properties of this factor(s) with other immunosuppressive substances such as immunoregulatory, immunoglobulin, etc.; and 5) Investigate factors responsible for enhancement of the immune response by other tumor systems (Sarcoma 37). The effect of suppressive cells and/or factors on the immune response will be studied at the cellular and molecular level by using chemically defined "T" dependent and "T" independent clinically relevant antigens; i.e., 2,4-dinitrophenyl (DNP) and pneumococcal polysaccharides (PnSSS) (initially SIII). The effect of factors on the in vivo and in vitro immune response will be determined by the PFC and RFC tests. The antibody response for DNP will be measured by precipitation by an 125I labelled immunoadsorbent. For PnSSS the highly sensitive radioimmunoassay will be used, which detects 1-10 mg of AbN/ml of serum. The effect of spleenectomy on enhancing or lifting the immunosuppression of the tumor-bearing mice will be investigated. The effect of the tumor on RES clearance of particulate 125I labelled pneumococcal vaccine will be investigated in normal, sham and spleenectomized mice in order to further delineate the immunological defect.